Cancer becomes life-threatening when tumor cells spread from the original tumor to other parts of the body. This spreading process depends not only on the cancer cells themselves, but also on the surrounding tissue called the extracellular matrix (ECM). The ECM provides physical support to cells. The structure and mechanical properties of ECM change with age and with diseases such as diabetes. These changes in ECM may make it easier for tumor cells to spread into healthy tissue, but the underlying mechanisms are not well understood. This project will study how aging- and diabetes-related changes in the ECM affect cancer cell invasion in breast cancer. The research will combine laboratory experiments with mathematical modeling to predict condition under which cancer cells are most likely to spread and metastasize. The project will also include education and outreach activities that will have broad societal impact. The project will train K-12 to graduate students in interdisciplinary research at the intersection of engineering and cancer biology. This project will establish a quantitative, energy-based framework for predicting tumor invasion as a function of ECM physical properties, with a particular emphasis on changes associated with aging and diabetes. Aging and diabetes alter key features of the ECM, including collagen concentration, crosslinking, stiffness, pore size, and structural anisotropy, creating complex mechanical environments that regulate cell behavior. However, existing studies report conflicting conclusions regarding how ECM mechanics influence cancer invasion, underscoring the need for a unifying physical framework. The project will integrate controlled experiments, thermodynamic modeling, and computational analysis to quantify the energetic barriers that govern whether cancer cells invade the surrounding matrix. By measuring how ECM physical properties regulate cellular forces, shape changes, and cell-matrix interactions, the research will comput